Anticancer effect of a pyrrole-imidazole polyamide-triphenylphosphonium conjugate selectively targeting a common mitochondrial DNA cancer risk variant in cervical cancer cells.

Cervical cancer remains a major threat to women's health, especially in countries with limited medical resources, and new drugs are needed to improve patient survival and minimize adverse effects. Here, we examine the effects of a triphenylphosphonium (TPP)-conjugated pyrrole-imidazole polyamide (CCC-h1005) targeting the common homoplasmic mitochondrial DNA (mtDNA) cancer risk variant (ATP6 8860A>G) on the survival of cervical cancer cell lines, cisplatin-resistant HeLa cells and patient-derived cervical clear cell carcinoma cells as models of cervical cancer treatment. We found that CCC-h1005 induced death in these cells and suppressed the growth of xenografted HeLa tumors with no severe adverse effects. These results suggest that PIP-TPP designed to target mtDNA cancer risk variants can be used to treat many cervical cancers harboring high copies of the target variant, providing a foundation for clinical trials of this class of molecules for treating cervical cancer and other types of cancers.

Anatomic Assessment of Petrous Internal Carotid Artery, Facial Nerve, and Cochlea Through the Anterior Transpetrosal Approach.

The aim of this study was to measure the related parameters of the cochlea, so as to allow preoperative assessment of the anatomic relationship of the petrous internal carotid artery (ICA), the facial nerve (FN), and the cochlea during skull base surgery. Seven parameters of these 3 structures were examined in the computed tomographic scan of 120 patients. The shortest distance from the cupula cochleae to the petrous ICA and the FN is as follows: 19.39 (1.01) mm to the stylomastoid foramen (D2), 10.27 (0.80) mm to the midpoint of the genu of FN canal (D3), 13.66 (0.88) mm to the exocranial opening of the carotid canal (D4), and 5.64 (1.03) mm to the midpoint of carotid knee (D5). The shortest distance between the mastoid segment of FN canal and the vertical segment of the petrous ICA (D6) was 13.33 (1.25) mm. The angle between D2 and D3 was measured at 45.66 (3.31)°, and the angle between D4 and D5 was measured at 41.08 (2.64)°. Clinically, it is relatively safe to work within the distances and angles measured in this research, and these results may give surgeons a practical and specific view of these 3 structures in the skull base approaches such as anterior transpetrosal approach to achieve the best possible surgical outcome and maximize safety.

Measurement of cochlea to facial nerve canal with thin-section computed tomographic image.

Facial nerve (FN) paralysis is a rare but devastating complication of cochlear implant surgery. This study aimed to measure the cupula of the cochlea to the tympanic segment of the FN canal, cupula of the cochlea to the mastoid segment of the FN canal, and the geniculate ganglion to provide a more secure and accurate orientation of the FN canal and to facilitate operation on the cochlea by avoiding potential damage to FN. Using computed tomography, we scanned skulls of 120 volunteers who suffer no cases of skull base lesions. Multiplane reconstruction images were prepared with high-resolution computed tomography. Preoperative evaluation of the FN anatomy within the temporal bone by high-resolution computed tomography helps in minimizing surgical trauma to the nerve, and these results can help guide clinical surgery on the cochlea.

Measurement of safety range in primary nasal transsphenoidal approach for pituitary surgery.

Although primary nasal transsphenoidal approach of pituitary surgery is widely used, no previous reports have determined the safety range of the surgery. The aim of our study was to clarify the medical reference range of safety angles and distances. One hundred forty-four (49 males, 95 females) participated in this study anonymously. We measured 4 parameters to achieve our goals, and the results are as follows: Angle 1 was 11.08 degrees for men and 11.31 degrees for women. Distance 1 was 17.22 mm for men and 16.46 mm for women. Angle 2 was 9.03 degrees for women and 8.73 degrees for men. Distance 2 was 14.54 mm for men and 14.10 mm for women. Angle 1 was 8.57 degrees for young, 8.93 degrees for adult, and 9.24 degrees for old. Distance 1 was 13.73 mm for young, 14.47 mm for adult, and 14.43 mm for old. Angle 2 was 11.24 degrees for young, 11.33 degrees for adult, and 11.10 degrees for old. Distance 2 was 16.86 mm for young, 16.90 mm for adult, and 16.39 mm for old. The differences in all 4 parameters were not statistically significant in comparison of sex and ages (P > 0.01). Hence, the 4 parameters that we determined contribute to the safety of the primary nasal transsphenoidal approach in pituitary surgery.

Ischemic postconditioning protects neuronal death caused by cerebral ischemia and reperfusion via attenuating protein aggregation.

OBJECTIVE: To investigate the effect of ischemic postconditioning on protein aggregation caused by transient ischemia and reperfusion and to clarify its underlying mechanism. METHODS: Two-vessel-occluded transient global ischemia rat model was used. The rats in ischemic postconditioning group were subjected to three cycles of 30-s/30-s reperfusion/clamping after 15 min of ischemia. Neuronal death in the CA1 region was observed by hematoxylin-eosin staining, and number of live neurons was assessed by cell counting under a light microscope. Succinyl-LLVY-AMC was used as substrate to assay proteasome activity in vitro. Protein carbonyl content was spectrophotometrically measured to analyze protein oxidization. Immunochemistry and laser scanning confocal microscopy were used to observe the distribution of ubiquitin in the CA1 neurons. Western blotting was used to analyze the quantitative alterations of protein aggregates, proteasome, hsp70 and hsp40 in cellular fractions under different ischemic conditions. RESULTS: Histological examination showed that the percentage of live neurons in the CA1 region was elevated from 5.21% ± 1.21% to 55.32% ± 5.34% after administration of ischemic postconditioning (P = 0.0087). Western blotting analysis showed that the protein aggregates in the ischemia group was 32.12 ± 4.87, 41.86 ± 4.71 and 34.51 ± 5.18 times higher than that in the sham group at reperfusion 12h, 24h and 48h, respectively. However, protein aggregates were alleviated significantly by ischemic postconditioning to 2.84 ± 0.97, 13.72 ± 2.13 and 14.37 ± 2.42 times at each indicated time point (P = 0.000032, 0.0000051 and 0.0000082). Laser scanning confocal images showed ubiquitin labeled protein aggregates could not be discerned in the ischemic postconditioning group. Further study showed that ischemic postconditioning suppressed the production of carbonyl derivatives, elevated proteasome activity that was damaged by ischemia and reperfusion, increased the expression of chaperone hsp70, and maintained the quantity of chaperone hsp40. CONCLUSION: Ischemic postconditioning could rescue significantly neuronal death in the CA1 region caused by transient ischemia and reperfusion, which is closely associated with suppressing the formation of protein aggregation.

Morphological study of transpterional-insula approach using volume rendering.

This study describes the measurements of inferior circular insular sulcus (ICIS) and the shortest distance from ICIS to the temporal horn and determines the position of the incision, which does less harm to the temporal stem in the transpterional-insula approach using volume-rendering technique. Results of the research showed that one-third point over the anterior side of ICIS may be the ideal penetration point during operation. And there is no difference between 2 hemispheres (P < 0.05). The comparison with the results of ICIS from other Chinese researches demonstrated that volume rendering is a reliable method in insular research that enables mass measurements.

An injectable adhesive antibacterial hydrogel wound dressing for infected skin wounds.

It's an exigent need for the improvement of novel antibacterial wound dressings with the increasing threats of drug resistance caused by excessive use of the antibiotics. In this work, an injectable, adhesive, hemostatic, biocompatible and bactericidal hydrogel wound dressing was fabricated. An injectable hydrogel can fill the irregular wound due to the characteristic of reversible sol-gel transition, whereas conventional dressings don't possess this ability. Oxidized alginate (ADA) and catechol-modified gelatin (Gel-Cat) were selected as the polymer backbones and they can crosslink in situ through double dynamic bonds, which were Schiff base and catechol-Fe coordinate bond; polydopamine decorated silver nanoparticles (PDA@Ag NPs) were also introduced into the hydrogel network. The double dynamic bonds endowed the hydrogel with injectable ability, shorter gelation time and enhanced mechanical property. And the aldehyde and catechol groups on the chains of ADA and Gel-Cat gave the hydrogel excellent adhesiveness. In addition, the PDA@Ag NPs in this system play two roles: one is bactericidal agent which can release from the hydrogel to kill the bacteria; the other is photothermal agent to convert 808 nm near-infrared light into heat to realize sterilization. In vitro study, the hydrogel displayed bactericidal ability against S. aureus and E. coli whether in photothermal antimicrobial test or agar diffusion test. In vivo test also testified that the hydrogel had a prominent therapeutic effect on infected wound through reducing inflammatory response and accelerating angiogenesis. Thus, we anticipate that our double dynamic bonds crosslinked hydrogel with PDA@Ag NPs as the antimicrobial agent can be a novel therapeutic way for infected wounds.

Construction of a Macrophage Infiltration Regulatory Network and Related Prognostic Model of High-Grade Serous Ovarian Cancer.

BACKGROUND: High-grade serous ovarian cancer (HGSOC) carries the highest mortality in the gynecological cancers; however, therapeutic outcomes have not significantly improved in recent decades. Macrophages play an essential role in the occurrence and development of ovarian cancer, so the mechanisms of macrophage infiltration should be elucidated. METHOD: We downloaded transcriptome data of ovarian cancers from the Gene Expression Omnibus and The Cancer Genome Atlas. After rigorous screening, 1566 HGSOC were used for data analysis. CIBERSORT was used to estimate the level of macrophage infiltration and WGCNA was used to identify macrophage-related modules. We constructed a macrophage-related prognostic model using machine learning LASSO algorithm and verified it using multiple HGSOC cohorts. RESULTS: In the GPL570-OV cohort, high infiltration level of M1 macrophages was associated with a good outcome, while high infiltration level of M2 macrophages was associated with poor outcomes. We used WGCNA to select genes correlated with macrophage infiltration. These genes were used to construct protein-protein interaction maps of macrophage infiltration. IFL44L, RSAD2, IFIT3, MX1, IFIH1, IFI44, and ISG15 were the hub genes in the network. We then constructed a macrophage-related prognostic model composed of CD38, ACE2, BATF2, HLA-DOB, and WARS. The model had the ability to predict the overall survival rate of HGSOC patients in GPL570-OV, GPL6480-OV, TCGA-OV, GSE50088, and GSE26712. In exploring the immune microenvironment, we found that CD4 memory T cells and activated mast cells showed that the degree of infiltration was higher in the high-risk group, while M1 macrophages were the opposite, and HLA molecules were overexpressed in the high-risk group. CONCLUSION: We constructed a macrophage infiltration-related protein interaction network that provides a basis for studying macrophages in HGSOC. Our macrophage-related prognostic model is robust and widely applicable. It predicts overall survival in HGSOC patients and may improve HGSOC treatment.

OLFML2B Is a Robust Prognostic Biomarker in Bladder Cancer Through Genome-Wide Screening: A Study Based on Seven Cohorts.

BACKGROUND: Bladder cancer lacks useful and robust prognostic markers to stratify patients at risk. Our study is to identify a robust prognostic marker for bladder cancer. METHODS: The transcriptome and clinical data of bladder cancer were downloaded from multiple databases. We searched for genes with robust prognosis by Kaplan-Meier analysis of the whole genome. CIBERSORT and TIMER algorithm was used to calculate the degree of immune cell infiltration. RESULTS: We identified OLFML2B as a robust prognostic marker for bladder cancer in five cohorts. Kaplan-Meier analysis showed that patients with a high level of OLFML2B expression had a poor prognosis. The expression of OLFML2B increased with the increase of stage and grade. We found that patients with high expression of OLFML2B still had a poor prognosis in two small bladder cancer cohorts. OLFML2B also has the prognostic ability in ten other tumors, and the prognosis is poor in high expression. The correlation analysis between OLFML2B and immune cells showed that it was positively correlated with the degree of macrophage infiltration and highly co-expressed with tumor-associated macrophage markers. Finally, the Wound-healing assay and Colony formation assay results showed that the migration and proliferation ability of bladder cancer cell lines decreased after the knockdown of OLFML2B. CONCLUSIONS: In summary, OLFML2B is a robust risk prognostic marker, and it can help patients with bladder cancer improve individualized treatment.

The surface modification of long carbon fiber reinforced polyether ether ketone with bioactive composite hydrogel for effective osteogenicity.

Long carbon fiber reinforced polyether ether ketone (LCFRPEEK) is fabricated using a three-dimensional (3D) needle-punched method in our previous work, which is considered as a potential orthopedic implant due to its high mechanical strength and isotropic properties, as well as having an elastic modulus similar to human cortical bone. However, the LCFRPEEK has inferior integration with bone tissue, limiting its clinical application. Thus, a facile surface modification method, using gelatin methacrylate/polyacrylamide composite hydrogel coating (GelMA/PAAM) loading with dexamethasone (Dex) on our newly-developed LCFRPEEK composite via concentrated sulfuric acid sulfonating and ultraviolet (UV) irradiation grafting methods, has been developed to tackle the problem. The results demonstrate that the GelMA/PAAM/Dex coating modified sulfonated LCFRPEEK (SCP/GP/Dex) has a hydrophilicity surface, a long-term Dex release capability and forms more bone-like apatite nodules in SBF. The SCP/GP/Dex also displays enhanced cytocompatibility and osteogenic differentiation in terms of rat bone marrow mesenchymal stem cells (rBMSCs) responses in vitro assay. The in vivo rat cranial defect assay confirms that SCP/GP/Dex boosts bone regeneration/osseointegration, which significantly improves osteogenic fixation between the implant and bone tissue. Therefore, the newly-developed LCFRPEEK modified via GelMA/PAAM/Dex bioactive coating exhibits improved biocompatibility and osteogenic integration capability, which has the basis for an orthopedic implant for clinical application.

Multidimensional Analyses of Tumor Immune Microenvironment Reveal the Possible Rationality of Immunotherapy and Identify High Immunotherapy Response Subtypes for Renal Papillary Cell Carcinoma.

Kidney renal papillary cell carcinoma (KIRP), the second most common subtype of renal cell carcinoma, still lacks effective treatment regimens for individualized immunotherapy because of the heterogeneity of its elusive immune microenvironment. Therefore, we aimed to comprehensively evaluate the immune microenvironment of KIRP by using the computational biology strategy to analyze the expression profile data of 289 KIRP patients obtained from The Cancer Genome Atlas database. Based on multidimensional, multi-omics bioinformatics analysis, we found that the tumor of patients with KIRP exhibited "hot" tumor characteristics but the CD8+ T cells in the tumor tissues did not limit tumor progression. Thus, patients with KIRP may realize higher clinical benefits by receiving treatment that can reverse CD8+ T-cell exhaustion. Among them, C1 and C3 immune subtypes could realize the best efficacy of reversing CD8+ T-cell exhaustion. Moreover, CCL5 and FASLG expression may be related to the formation of the immunosuppressive microenvironment in the tumors of patients with KIRP. In conclusion, the immune microenvironment landscape presented in this study provides a novel insight for further experimental and clinical exploration of tailored immunotherapy for patients with KIRP.

A bi-layered scaffold of a poly(lactic-co-glycolic acid) nanofiber mat and an alginate-gelatin hydrogel for wound healing.

A resveratrol-loaded bi-layered scaffold (RBS) that consists of a resveratrol-loaded poly(lactic-co-glycolic acid) (Res-PLGA) electrospinning nanofiber mat (upper layer) and an alginate di-aldehyde (ADA)-gelatin (GEL) crosslinking hydrogel (ADA-GEL) (lower layer) was fabricated as a wound dressing material. It was made through mimicking the epidermis and dermis of the skin. The RBS exhibited good hemostatic ability and proper swelling ability. Furthermore, HaCaT cells and human embryonic skin fibroblasts (ESFs) were also cultured in the nanofiber layer and hydrogel layer of RBS, and the results indicated that both HaCaT and ESFs could grow well in the materials. The in vivo experiment using a Sprague-Dawley (SD) rat skin wound as a model showed that the RBS could accelerate the wound healing rate compared with the Res-PLGA group and ADA4-GEL6 group. These results indicated that this resveratrol-loaded bi-layered scaffold can be a potential candidate in promoting wound healing.

Postoperative discal pseudocyst and its similarities to discal cyst: A case report.

BACKGROUND: Postoperative discal pseudocyst (PDP) is a rare condition that presents after surgery for lumbar disc herniation. Due to the lack of information, the diagnosis and treatment of PDP remain controversial. Herein, we report a PDP case that occurred following percutaneous endoscopic lumbar discectomy and received conservative treatment. Additionally, we review all the published literature regarding PDP and propose our hypothesis regarding PDP pathology. CASE SUMMARY: A 23-year-old man presented with a relapse of low back pain and numbness in his left lower extremity after undergoing percutaneous endoscopic lumbar discectomy for lumbar disc herniation. Repeat magnetic resonance imaging demonstrated a cystic lesion at the surgical site with communication with the inner disc. The patient was diagnosed as having PDP. The patient received conservative treatment, which resulted in rapid improvement and spontaneous regression of the lesion, and had a favorable outcome in follow-up. CONCLUSION: PDP and discal cyst (DC) exhibit similarities in both histological and epidemiological characteristics, which indicates the same pathological origin of PDP and DC. The iatrogenic annular injury during discectomy might accelerate the pathological progression of DC. For patients with mild to moderate symptoms, conservative treatment can lead to great improvement, even inducing spontaneous regression. However, surgical cystectomy is necessary in patients with neurological deficits and where conservative treatment is ineffective.

A Review of Clinicopathological Characteristics and Treatment of Solid Pseudopapillary Tumor of the Pancreas with 2450 Cases in Chinese Population.

BACKGROUND: Solid pseudopapillary tumor of the pancreas (SPTP) has been reported as a rare disease with low malignant potential. The aim of this study was to summarize experiences of the diagnosis and treatment for the patients reported in the Chinese population. METHOD: 2450 SPTP cases reported in English and Chinese literature before Jan 2020 were for our review and analysis retrospectively. RESULT: There are 389 male cases and 2061 female cases, and the ratio of male/female was 1 : 5.3. The average age was 29.3 years. The main clinical symptoms were upper abdominal pain and bloating discomfort in 51.6% of the cases and epigastric mass. 38.6% of the tumor was located at the head of the pancreas and 55.4% at the body and tail of the pancreas. The most frequent operative styles were tumor enucleation (38.4%). Pathology showed that the average diameter of the tumor was 8.2 cm and 12.3% of SPTP was malignant. 98.3% of cases had favorable survival. CONCLUSIONS: SPTP is a rare indolent tumor occurring mainly in young women, and the main clinical performances are abdominal mass and abdominal pain; most tumors are distributed at the head and the tail of the pancreas; the prognosis after complete resection is excellent.

Staged treatment and internal fixation of floating ankle: A case report and literature review.

RATIONALE: Floating ankle is a rare traumatic condition characterized by a combination of tibial and ipsilateral foot fractures, with the ankle remaining intact. It is usually caused by high-energy trauma and also presents with serious soft tissue damage. Its treatment is mainly restricted to external fixation, which results in poor outcomes. We present a patient with a floating ankle who underwent staged treatment and achieved full internal fixation, subsequently returning to normal activity. PATIENT CONCERNS: A 26 year- old man had an accident with an reel machine and sustained an open fracture on his right lower extremity. DIAGNOSES: Digital radiograph demonstrated a distal tibial fracture, fibular fracture, and multiple metatarsal fractures, which fulfilled the criteria for a floating ankle. INTERVENTIONS: Initial ankle-spanning external fixation was performed. After 21 days, the patient underwent open reduction and internal fixation on his first and fifth metatarsals, and K-wire fixation on his fourth metatarsal. The external fixator was replaced by plaster fixation. Seven days later, the patient underwent internal fixation of his leg, open reduction and internal fixation with plating was applied of the fibular fracture, and minimally invasive plate osteosynthesis of the tibial fracture. OUTCOMES: At 1-year follow-up, bone union was identified by digital radiograph; after 2 years, his ankle function had fully recovered, and he resumed his normal activities. LESSONS: In the staged treatment protocol of the floating ankle, temporary external fixation provided traction and immobilization of the skeletal and soft tissues. Secondary internal fixation maintained the reduction and alignment and allowed early exercise, which is critical to the prognosis of a floating ankle.

Three-Dimensional Coating of SF/PLGA Coaxial Nanofiber Membranes on Surfaces of Calcium Phosphate Cement for Enhanced Bone Regeneration.

Calcium phosphate cements (CPCs) have been widely used for the study of bone regeneration because of their excellent physical and chemical properties, but poor biocompatibility and lack of osteoinductivity limit potential clinical applications. To overcome these limitations, and based on our previous research, CPC scaffolds were prepared with CPC as the principal material and polyethylene glycol (PEG) as a porogen to introduce interconnected macropores. Using a bespoke electrospinning auxiliary receiver, silk fibroin (SF)/poly(lactide-co-glycolide) (PLGA) coaxial nanofibers containing dexamethasone (DXM) and recombinant human bone morphogenetic protein-2 (rhBMP2) were fabricated which were coated on the surface of the CPC. By comparing the surface morphology by SEM, hydrophilicity, results of FTIR spectroscopy, and mechanical properties of the composite materials fabricated using different electrospinning times (20, 40, 60 min), the CPC surface constructed by electrospinning for 40 min was found to exhibit the most appropriate physical and chemical properties. Therefore, composite materials were built for further study by electrospinning for 40 min. The osteogenic capacity of the SF/PLGA/CPC, SF-DXM/PLGA/CPC, and SF-DXM/PLGA-rhBMP2/CPC scaffolds was evaluated by in vitro cell culture with rat bone marrow mesenchymal stem cells (BMSCs) and using a rat cranial defect repair model. ALP activity, calcium deposition levels, upregulation of osteogenic genes, and bone regeneration in skull defects in rats with SF-DXM/PLGA-rhBMP2/CPC implants were significantly higher than in rats implanted with the other scaffolds. These results suggest that drug-loaded coaxial nanofiber coatings prepared on a CPC surface can continuously and effectively release bioactive drugs and further stimulate osteogenesis. Therefore, the SF-DXM/PLGA-rhBMP2/CPC scaffolds prepared in this study demonstrated the most significant potential for the treatment of bone defects.

Paclitaxel and etoposide-loaded Poly (lactic-co-glycolic acid) microspheres fabricated by coaxial electrospraying for dual drug delivery.

In this study, we fabricated paclitaxel (PTX) and etoposide (ETP) loaded Poly (lactic-co-glycolic acid) (PLGA) microspheres with core-shell structures and particle sizes ranging from 1 to 4 µm by coaxial electrospraying. The microspheres were analyzed by scanning electron microscopy (SEM), transmission electron microscopy (TEM). The drug loading rate and entrapment efficiency of the microspheres were detected by high performance liquid chromatograph (HPLC). Moreover, the drug release profiles and degradation of drug-loaded PLGA microspheres in vitro were investigated, respectively. The distinct layered structure that existed in the manufactured core-shell microspheres can be observed by TEM. The in vitro release profiles indicated that the PLGA/PTX + ETP (PLGA/PE) microspheres exhibited the controlled release of two drugs in a sequential manner. Cell Counting Kit-8 was used to detect the toxic and side effects of the microspheres on bone tumor cells. PTX and ETP for combination drug therapy loaded microspheres had more cytotoxic effect on saos-2 osteosarcoma cells than the individual drugs. In conclusion, core-shell PLGA microspheres by electrospraying for combination drug therapy is promising for medicine applications, the PLGA/PE microspheres have some potential for osteosarcoma treatment.

Thermo/pH dual-responsive core-shell particles for apatinib/doxorubicin controlled release: preparation, characterization and biodistribution.

Dual-drug loaded and dual-responsive core-shell particles (DD particles) were synthesized via an electrospray method in one step. First, 4-CBS-chitosan was synthesized by conjugating an aromatic sulfonamide group at the C2-N position of chitosan. Then, poly(nisopropylacylamide) (PNIPAM) containing apatinib model drug solution as the outer solution and 4-CBS-chitosan containing doxorubicin (DOX) as the inner solution were injected through a coaxial tube into a high voltage electric field. The formulation conditions of the DD particles were tuned to obtain spherical particles with narrow size distributions (94.97 ± 33.75 nm in diameter). The particles showed excellent responses to changes in pH and temperature: the releases of entrapped apatinib and doxorubicin (DOX) were accelerated when the solution temperature was above its lower critical solution temperature (LCST) (34 °C) or when the solution pH was acidic (pH 1.2). Degradation studies indicated that the DD particles degraded; the inner layer sank and the outer layer fragmented. In vivo biodistribution was studied by intragastric administration; it was found that the retention time of the drugs in the stomach was significantly improved and the initial burst release decreased, while a higher drug concentration level was maintained for a long time. These particles can exploit triggering mechanisms for release of the entrapped drugs from the particles, indicating their great potential for use in controlled release applications.

Long noncoding RNA TOB1-AS1, an epigenetically silenced gene, functioned as a novel tumor suppressor by sponging miR-27b in cervical cancer.

Cervical cancer is one of the most common cancers in females, accounting for a majority of cancer-related deaths in worldwide. Long non-coding RNAs (lncRNAs) have been identified as critical regulators in many tumor-related biological processes. Thus, investigation into the function and mechanism of lncRNAs in the development of cervical cancer is very necessary. In this study, we found that the expression of TOB1-AS1 was significantly decreased in cervical cancer tissues compared with the adjacent normal tissues. The methylation status of TOB1-AS1-related CpG island was analyzed using methylation specific PCR and bisulfite sequencing analysis, revealing that the aberrant hypermethylation of TOB1-AS1-related CpG island was frequently observed in primary tumors and cervical cancer cells. The expression of TOB1-AS1 in cervical cancer cells could be reversed by demethylation agent treatment. Functionally, overexpression of TOB1-AS1 significantly inhibited cell proliferation, cell cycle progression, invasion and induced apoptosis, while knockdown of TOB1-AS1 exhibited the opposite effect. Furthermore, it was determined that TOB1-AS1 was able to bind and degrade the expression of miR-27b. Upregulation of miR-27b promoted cell growth, cell cycle transition from G1 phase to S phase, and invasion and reduced apoptosis, phenomenon could be reversed by TOB1-AS1. Inhibition of miR-27b attenuated the promotive effect of si-TOB1-AS1 on cellular processes. Upregulation of TOB1-AS1 also suppressed tumor growth in vivo. Clinically, methylation of TOB1-AS1 and low expression of TOB1-AS1 was significantly correlated with tumor stage and tumor size, respectively. Univariate and multivariate analyses confirmed that low level of TOB1-AS1 was an independent risk factor for death. In conclusion, we suggested that the epigenetically silenced TOB1-AS1 was unable to restrain miR-27b, which contributed to cervical cancer progression.

Prognostic value of programmed death-ligand 1 in sarcoma: a meta-analysis.

BACKGROUND: The prognostic role of programmed death-ligand 1 (PD-L1) in sarcoma remains controversial. We performed a meta-analysis so as to investigate the impact of PD-L1 on clinicopathlogical findings and survival outcomes in sarcoma. MATERIALS AND METHODS: A comprehensive search in PubMed, Embase and the Cochrane Library was conducted for relevant studies. The odds ratios or hazard ratios, at 95% confidence intervals were used as measures for investigation of the correlation between PD-L1 expression and clinicopathlogical features or survival outcomes. RESULTS: Fourteen eligible studies comprising 868 patients were selected for analysis. Pooled hazard ratios indicated that the association of PD-L1 expression with overall survival in bone sarcoma (osteosarcoma and chondrosarcoma) patients was statistically significant (1.987, 95% CI: 1.224-3.224, p = 0.005), as was its association with event-free survival in bone and soft-tissue sarcoma patients (3.868, 95% CI: 2.298-6.511, p = 0.000). Additionally, the expression of PD-L1 was positively correlated with the infiltration of programmed death 1 (PD-1) positive T-lymphocytes (OR: 4.012, 95% CI: 2.391-6.733, p = 0.000). CONCLUSIONS: Our meta-analysis indicated that high PD-L1 expression is likely to be a negative factor for patients with sarcomas and that it predicts worse survival outcomes.